August 16, 2012

Our big human brains may depend on DUF1220 copy numbers

This is quite remarkable, notice how Neandertals who were bigger-brained than living humans had a higher DUF1220-domain copy number (as estimated from the Green et al. 2010 data).

Certainly wondering how many DUF1220-domain copies I have :) My running estimate using my own calculator is that I have 1,493gr worth of brain, which isn't Amud- or Turgenev-worthy, but quite respectable, and which ought to translate into plenty of DUF1220 copies; I guess I'll have to wait until full genome sequencing costs drop a little more before I can find out.

The human brain, with its unequaled cognitive capacity, evolved rapidly and dramatically.

"We wanted to know why," says James Sikela, PhD, who headed the international research team that included researchers from the University of Colorado School of Medicine, Baylor College of Medicine and the National Institutes of Mental Health. "The size and cognitive capacity of the human brain sets us apart. But how did that happen?"

"This research indicates that what drove the evolutionary expansion of the human brain may well be a specific unit within a protein – called a protein domain -- that is far more numerous in humans than other species."

The protein domain at issue is DUF1220. Humans have more than 270 copies of DUF1220 encoded in the genome, far more than other species. The closer a species is to humans, the more copies of DUF1220 show up. Chimpanzees have the next highest number, 125. Gorillas have 99, marmosets 30 and mice just one. "The one over-riding theme that we saw repeatedly was that the more copies of DUF1220 in the genome, the bigger the brain. And this held true whether we looked at different species or within the human population."

From the paper:

Among primate lineages, there is a high correlation between DUF1220 copy number (the highest copy number, greater than 270, was found in Homo sapiens [human and Neanderthal]) and increased brain size ... as well as an increased number of cortical neurons ... Taken together, these observations support the view that DUF1220-domain copy number, i.e., DUF1220-domain dosage, functions as a general effector of evolutionary, pathological, and normal variation in brain size.

The American Journal of Human Genetics, 16 August 2012
doi:10.1016/j.ajhg.2012.07.016

DUF1220-Domain Copy Number Implicated in Human Brain-Size Pathology and Evolution

Laura J. Dumas

DUF1220 domains show the largest human-lineage-specific increase in copy number of any protein-coding region in the human genome and map primarily to 1q21, where deletions and reciprocal duplications have been associated with microcephaly and macrocephaly, respectively. Given these findings and the high correlation between DUF1220 copy number and brain size across primate lineages (R2 = 0.98; p = 1.8 × 10−6), DUF1220 sequences represent plausible candidates for underlying 1q21-associated brain-size pathologies. To investigate this possibility, we used specialized bioinformatics tools developed for scoring highly duplicated DUF1220 sequences to implement targeted 1q21 array comparative genomic hybridization on individuals (n = 42) with 1q21-associated microcephaly and macrocephaly. We show that of all the 1q21 genes examined (n = 53), DUF1220 copy number shows the strongest association with brain size among individuals with 1q21-associated microcephaly, particularly with respect to the three evolutionarily conserved DUF1220 clades CON1(p = 0.0079), CON2 (p = 0.0134), and CON3 (p = 0.0116). Interestingly, all 1q21 DUF1220-encoding genes belonging to the NBPF family show significant correlations with frontal-occipital-circumference Z scores in the deletion group. In a similar survey of a nondisease population, we show that DUF1220 copy number exhibits the strongest correlation with brain gray-matter volume (CON1, p = 0.0246; and CON2, p = 0.0334). Notably, only DUF1220 sequences are consistently significant in both disease and nondisease populations. Taken together, these data strongly implicate the loss of DUF1220 copy number in the etiology of 1q21-associated microcephaly and support the view that DUF1220 domains function as general effectors of evolutionary, pathological, and normal variation in brain size.

Brain size relative to body weight, rather than absolute brain size, appears to be the best crude physiological proxy for intelligence. DUF1220 copy number does seem to corrolate with brain size, but one needs to massage the numbers before one can make a meaningful estimate about how that would manifest behaviorially.

Any way you cut it, Neanderthals still had big brains, for example, relative to Gorillas. But, as Neanderthals were a bit more robust than modern humans, it wouldn't be surprising if their brain size relative to body size was the same or slightly less than modern humans.

Size also doesn't necessarily capture dimensions of brain organization like plasticity (i.e. how much of the brain is hard wired and how much it can adapt), something that for modern humans changes at different points in the life cycle. There is suggestive evidence that Neanderthals may have been less plastic than modern humans in how their brains were organized.

"Body size, expressed as height or stature, is an important determinant of many other biological variables. Thus, it is surprising that many textbooks portray a wrong picture of Neanderthal height as being "very short" or "just over 5 feet". Based on 45 long bones from maximally 14 males and 7 females, Neanderthals' height averages between 164 and 168 (males) resp. 152 to 156 cm (females). This height is indeed 12-14 cm lower than the height of post-WWII Europeans, but compared to Europeans some 20,000 or 100 years ago, it is practically identical or even slightly higher. Considering the body build of Neanderthals, new body weight estimates show that they are only slightly above the cm/weight or the Body Mass Index of modern Americans or Canadians. The calculation of the relative surface area (approximately 240-244 cm2/kg) is very low and supports earlier findings of a morphological and anatomical thermoregulatory adaptation to a cold climate in the Neanderthals."

Since the Neandertals died out so long ago, I think it unfair to assume they'd be inferior to us in any way had they survived. If their brains were larger, it's possible they'd have evolved more sophisticated survival methods, languages, arts, etc., than homo sapiens sapiens.

"Size also doesn't necessarily capture dimensions of brain organization like plasticity (i.e. how much of the brain is hard wired and how much it can adapt), something that for modern humans changes at different points in the life cycle. There is suggestive evidence that Neanderthals may have been less plastic than modern humans in how their brains were organized".

There is possibly some truth in what you say but I think, as I've said before, you are inclined to emphasise the difference between moderns and Neanderthals rather than consider the similarities.

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